Immune Assignment #2

Question 1

Describe the phagocytic ability of monocytes

Answer 1

have limited phagocytic activity

Question 2

Describe the phagocytic ability of macrophages

Answer 2

are specialized phagocytes

Question 3

Describe the phagocytic ability of neutrophils

Answer 3

have exceptional phagocytic ability

Question 4

Describe differentiation of monocytes in bone marrow

Answer 4

CCL/MCP-1 (Monocyte chemotatic factor-1) attracts monocytes into circulation and into tissues.
Activated monocytes secrete cytokines (GM-CSF, G-CSF, and M-CSF

Question 5

Monocytes secrete GM-CSF, G-CSF, and M-CSF. describe the role of each

Answer 5

GM-CSF: Role in differentiation of a myeloid progenitor to a GM progenitor.
G-CSF: Role in differentiation of a myeloid progenitor to a granulocyte in hematopoiesis
M-CSF: Role in differentiation of a myeloid progenitor to a monocyte in hematopoiesis.

Question 6

Explain the role of CCL2/MCP-1.

Answer 6

Mobilization and chemotaxis to site of inflammation

Question 7

Effect of GM-CSF on dendritic cells

Answer 7

Enhances dendritic cell maturation, proliferation and migration

Question 8

Describe macrophages with respect to: differentiation from monocytes

Answer 8

Monocytes enter circulation

Monocytes leave circulation and enter tissues and become macrophages

Question 9

Describe macrophages with respect to: role of MCP-1/CCL-2 in absence and during infection

Answer 9

Chemokine CCL-2/MCP-1 enhances recruitment of monocytes into circulation and migration into tissues where they differentiate into macrophages (during infection)

Question 10

list the names of macrophages as a function of tissue

Answer 10

CNS ---> Microglial cells 
Liver ---> Kupffer cells 
Synovium ----> Synoviocytes 
Lung ---> Alveolar macrophages 
Lymph and spleen ---> macrophages

Question 11

List the two main roles of macrophages

Answer 11

1. Phagocytosis (direct regonition, indirect recognition and leads to cytokine and chemokine secretion)
2. Antigen presenting cells for CD4 + T cells
   (remember not as effective as dendritic cells)

Question 12

Recognition of antigens/pathogens is direct or indirect. Explain the term direct recognition

Answer 12

very simply —> immediate recognition of a pathogen by a phagocyte

Question 13

Explain the role of pattern recognition receptors on phagocytes

Answer 13

PRRs (pattern recognition receptors) interact directly with pathogens via PAMPs (pattern associated molecular patterns)
PRRs distinguish pathogens from self. PRRs exist as membrane bound receptors, cytosolic receptors, or secreted receptors. These receptors trigger cascades of biochemical events that lead to secretion of inflammatory cytokines, and other cellular responses associated with innate immune responses.

Question 14

Name one family of proteins that are classed as PRRs

Answer 14

a group of membrane bound receptors that exist both as cytosolic vesicles and external cell membranes are the toll like receptors (TLRs)

Question 15

Explain the role of pathogen associated molecular patterns on pathogens (PAMPs)

Answer 15

Ligands, or molecules expressing the molecular patterns on pathogens.
PRRs interact directly with pathogens via PAMPs.

Question 16

Describe the steps in phagocytosis and formation of phagosome.

Answer 16

Phagocytosis is a process of internalization and degradation. Recognition and binding of the pathogen is followed by its ingestion as a portion of a plasma membrane extends outward and surrounds the microbe.
This extension outward and surround of the microbe forms a phagocytic vacuole termed phagosome.

Question 17

Describe the steps in formation of a phagolysosome

Answer 17

Lysosomes, present in the cytosol, fuse with the phagosome to form a fusion product, the phagolysosome, into which lysosomal granules are discharged.

Question 18

List the armamentarium generated from NAPDH oxidase

Answer 18

Superoxide (forms hydrogen peroxide)
Hydrogen Peroxide 
Hydroxyl Radical 
Hydroxyl Ion 
Hypochlorite (source myeloperoxidase); a potent anti-microbial agent

Question 19

List the armamentarium generated from lysosomal fusion

Answer 19

Lactoferrin
lysozyme
defensins
Myeloperoxidase (produces hypochlorite)

Question 20

List the armamentarium generated from iNOS

Answer 20

inducible nitric oxide synthase

product: NO and other RNIs

Question 21

Describe the effect of IFNgamma on macrophage activation and the source of these cytokines

Answer 21

1. Role in NAPDH oxidase and iNOS activity (enhances NADPH oxidase activity and activates iNOS)
2. Source —> secreted by NK cells and secreted by Th1 cells (main producer)

Question 22

Describe the effect of TNF on macrophage activation and the source of these cytokines

Answer 22

1. Role in NADPH oxidase and iNOS activity (enhances NADPH oxidase activity and role in iNOS activation)
2. Source —> secreted by macrophages and Th1 cells (main producer)

Question 23

Describe the effect of IL-4, IL-10 and TGFB on macrophage activation and the source of these cytokines

Answer 23

1. Role in iNOS downregulation (down regulate iNOS; TGFB is most effective)
2. Source —> TGFB is secreted by Th2 cells and macrophages. IL-10 and IL-4 are secreted by Th2 cells

Question 24

List the chemokines secreted by activated macrophages

Answer 24

Activated macrophages secrete chemokines IL-8/CXCL8 and MCP-1/CCL2 (target cells —>neutrophils and monocytes, respectively) (role –> chemotactic)

Question 25

List the cytokines secreted by activated macrophages

Answer 25

IL-1 + TNF ----> target cells are vascular endothelial cells and the role induces vascular endothelial to secrete CXCL-8 (IL-8) and MCP-1 (CCL2). TGFB ---> target cells are iNOS, Th17 cells and a/i Treg cells and its role is to down regulate iNOS phagocytes IL-6 ---> target cells are hepatocytes and Thp cells and its role is to bind to hepatocytes to secrete C-reactive protein (CRP) IL-12 ---> Target is NK cells but role is to activate NK cells to secrete IFNgamma IL-15/IL-18 ---> target cells NK cells and role is to enhance IFNgamma secretion induced by IL12 IL-23 ---> target cells Th17 cells and its role is stabilization of Th17 cells during differentiation of Thp cells to Th17 cells.

Question 26

Describe the inflammasome

Answer 26

The NALP3 inflammasome is a large multi-protein complex that plays a critical role in the host defense by mediating the conversion of the zymogen, procaspase-1 to caspase-1. Caspase-1 converts pro-IL-1 and and pro-IL-18 to biologically active forms (IL-1 and IL-18) which are secrete from the macrophage.

Question 27

Describe the signal 1 and signal 2 in the inflammasome

Answer 27

The release of IL-1 and IL-18 is a two signal process: (i) signal 1 is activation of NFkB following PAMP binding to PRR, which leads to transcription of pro-IL-1 and pro-IL-18. (ii) signal 2 from DAMP causes the conversion of pro-caspase 1 to caspase-1. Caspase-1 then cleaves the biologically active precursors to their active forms IL-1 and IL-18, which are then secreted from the cells

Question 28

List 5 examples of DAMPS

Answer 28

Molescules that trigger signal 2 are referred to as danger associated molecular patterns (DAMPS). (i) numerous molecule released during trauma or cell death. (ii) reactive oxygen species, (iii) ATP, (iv) cholesterol crystals, (v) free fatty acids

Question 29

Describe the role of IL-1 and TNF on vascular endothelium in an inflammatory response

Answer 29

Secreted by macrophages --> synergistic effect ILF and TNF ---> (i) secrete CXCL8 (IL-8) and MCP-1 (CCL2); (ii) express E selectin, VCAM-1 and ICAM-1; (iii) upregulate expression of ICAM-2. VCAM-1 on vascular endothelium interaction with VLA-4 on monocytes, lymphocytes, and eosinophils. ICAM-1 and ICAM-2 on vascular endothelium interact with LFA-1 on neutrophils, monocytes, lymphocytes and eosinophils

Question 30

List the three opsonins that may be deposited on a pathogen. list their receptors as well

Answer 30

1. FCgammaR -----> IgG 2. CR-1 (complement receptor) ---> C3b 3. CRP binding site ---> CRP (note receptors are on the phagocyte)

Question 31

Explain how the opsonins were generated

Answer 31

Opsonins are generated when components other than phagocytes are activated in response to the pathogen

Question 32

Explain why opsonin-mediated recognition is called indirect recognition

Answer 32

Follows antibody production!! Phagocytes recognize pathogens indirectly using cell surface receptors that recognize molecules that have bound to, or been deposited, on the pathogen cell surface

Question 33

Explain the consequence of CD200R interaction with CD200

Answer 33

Phagocyte responses are regulated by multiple factors as well as by cell surface receptors, including inhibitory signals resulting from ligation CD200R by the widely distributed membrane protein, CD200.

Question 34

Is CD200R on the cell being sent a negative signal or the cell sending the negative signal?

Answer 34

CD200R is on the cell being sent the negative signal

Question 35

Explain why macrophages are not as effective as antigen presenting cells as dendritic cells

Answer 35

Secondary immune responses generally occur at the site of infection, while, primary immune responses occur in secondary lymphoid tissues and not at the site of infection. Dendritic cells can actually capture antigen in the periphery and transport it to the appropriate lymphoid tissue

Question 36

For antigen presentation by macrophages

Answer 36

Antigen presenting cells (present) antigen fragments to CD4 T cells.

Question 37

Describe neutrophils

Answer 37

1. Do not function as antigen presenting cells 2. Do not secrete cytokines or chemokines 3. Recognition is the same as that described for macrophages 4. Armamentarium products and functions are that as described for macrophages.

Question 38

Neutrophils- differentiation

Answer 38

Neutrophils mature from precursor cells in the bone marrow under influence of G-CSF

Question 39

Neutrophils- percent circulating leukocytes

Answer 39

60% of circulating leukocytes in peripheral blood

Question 40

Neutrophils- half life in circulation

Answer 40

Once neutrophils are released into circulation they have a half life of some 8 hours

Question 41

Neutrophils- chemotatic factors that attract neutrophils to site of inflammation

Answer 41

A number of chemotactic factors (IL-8/CXCL8 and C5a) generated in the early phase of an inflammatory response result in enhanced release of neutrophils from the bone marrow and attraction to the site of inflammation.